Assessing the neural basis of uncertainty in perceptual category learning through varying levels of distortion.

The formation of new perceptual categories involves learning to extract that information from a wide range of often noisy sensory inputs, which is critical for selecting between a limited number of responses. To identify brain regions involved in visual classification learning under noisy conditions, we developed a task on the basis of the classical dot pattern prototype distortion task [M. I.

Differential effects of serotonergic and noradrenergic antidepressants on brain activity during a cognitive control task and neurofunctional prediction of treatment outcome in patients with depression.

Background: We investigated the differential effects of serotonergic and noradrenergic antidepressants on brain activation in patients with major depressive disorder during a Stroop task. We predicted that pretreatment hyperactivity in the rostral anterior cingulate cortex would predict better treatment outcomes.

Methods: In total, 20 patients underwent naturalistic open-label clinical treatment with citalopram (n = 12) or reboxetine (n = 8).

Reactive oxygen species abrogate the anticarcinogenic effect of eicosapentaenoic acid in Atm-deficient mice.

Recent studies have demonstrated that n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) are able to suppress cell proliferation and inhibit tumor growth. The objective of our study was to investigate the influence of a high dose EPA on the development of the tumor phenotype in ataxia-telangiectasia mutated (Atm)-deficient mice, a genetic cancer model that is associated with increased levels of oxidative stress. We analyzed toxicity, proliferation, cell-cycle progression, and apoptosis of EPA in vitro and latency to tumorigenesis in vivo.

Intact indoleamine 2,3-dioxygenase activity in human chronic granulomatous disease.

Chronic granulomatous disease (CGD) is characterized by a disability to produce reactive oxygen intermediates (ROI) caused by a defect of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. A hyperinflammatory response to immune activation has been reported to contribute to the pathology of CGD. The tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is considered critical for regulating immune responses and suppression of inflammation.

Accuracy and reproducibility of a novel semi-automatic segmentation technique for MR volumetry of the pituitary gland.

Introduction: Although several reports about volumetric determination of the pituitary gland exist, volumetries have been solely performed by indirect measurements or manual tracing on the gland's boundaries. The purpose of this study was to evaluate the accuracy and reproducibility of a novel semi-automatic MR-based segmentation technique.

Methods: In an initial technical investigation, T1-weighted 3D native magnetised prepared rapid gradient echo sequences (1.

Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease.

Chronic granulomatous disease (CGD) is an inherited disorder characterized by recurrent infections and deregulated inflammatory responses. CGD is caused by mutations in subunits of the NADPH oxidase, an enzyme that generates reactive oxygen species in phagocytes. To elucidate the contribution of the proinflammatory protease caspase-1 to aberrant inflammatory reactions in CGD, we analyzed cells isolated from patients with defects in the phagocyte oxidase subunits p22phox, p47phox or gp91phox.

Signed outside: a surface marker system for transgenic cytoplasmic proteins.

Chronic granulomatous disease is a primary immunodeficiency, comprising five molecular defects, characterized by an impaired respiratory burst activity of myeloid cells. We are currently developing a gene therapy vector for the p47phox-deficient form of chronic granulomatous disease. Classic intracellular immunostaining of the cytoplasmic p47phox transgene product, however, interferes with respiratory burst activity.

Complex pattern of cortical thinning in schizophrenia: results from an automated surface based analysis of cortical thickness.

A considerable body of evidence from structural brain imaging studies suggests that patients with schizophrenia have significant alterations of gray matter density. Additionally, recently developed surface-based analysis approaches demonstrate reduced cortical thickness in patients with schizophrenia. However, the number of studies employing this relatively new method is still limited.

Validation of quantitative estimation of tissue oxygen extraction fraction and deoxygenated blood volume fraction in phantom and in vivo experiments by using MRI.

The blood oxygenation level dependent signal of cerebral tissue can be theoretically derived using a network model formed by randomly oriented infinitely long cylinders. The validation of this model by phantom and in vivo experiments is still an object of research. A network phantom was constructed of solid polypropylene strings immersed in silicone oil, which essentially eliminated the effect of spin diffusion.

Structure-function relationships in the context of reinforcement-related learning: a combined diffusion tensor imaging-functional magnetic resonance imaging study.

In the context of probabilistic learning, previous functional magnetic resonance imaging studies have shown decreasing uncertainty accompanying decreasing neuronal activation in task-relevant networks. Moreover, initial evidence points to a relationship between white matter structure and cognitive performance. Little is known, however, about the structural correlates underlying individual differences in activation and performance in the context of probabilistic learning.

Whole-brain mapping of venous vessel size in humans using the hypercapnia-induced BOLD effect.

Measuring the morphology of the cerebral microvasculature by vessel-size imaging (VSI) is a promising approach for clinical applications, such as the characterization of tumor angiogenesis and stroke. Despite the great potential of VSI, this method has not yet found widespread use in practice due to the lack of experience in testing it on healthy humans. Since this limitation derives mainly from the need for an invasive injection of a contrast agent, this work explores the possibility to employ instead the easily accessible blood oxygenation level dependent (BOLD) effect for VSI of the venous microstructure.

Fronto-cingulate effective connectivity in obsessive compulsive disorder: a study with fMRI and dynamic causal modeling.

Evidence suggests that obsessive compulsive disorder (OCD) is associated with an overactive error control system. A key role in error detection and control has been ascribed to the fronto-cingulate system. However, the exact functional interplay between the single components of this network in OCD is largely unknown.

Influence of anisotropic electrical conductivity in white matter tissue on the EEG/MEG forward and inverse solution. A high-resolution whole head simulation study.

To investigate the influence of anisotropic electrical conductivity in white matter on the forward and inverse solution in electroencephalography (EEG) and magnetoencephalography (MEG) numerical simulation studies were performed. A high-resolution (1 mm3 isotropic) finite element model of a human head was implemented to study the sensitivity of EEG and MEG source localization. In vivo information on the anisotropy was obtained from magnetic resonance diffusion tensor imaging and included into the model, whereas both a direct transformation and a direct transformation with volume normalization were used to obtain conductivity tensors.

Attenuation of cerebral venous contrast in susceptibility-weighted imaging of spontaneously breathing pediatric patients sedated with propofol.

Background And Purpose: SWI is known for its detailed visualization of the cerebral venous system and seems to be a promising tool for early detection of cerebrovascular pathologies in children, who are frequently sedated for MR imaging. Because sedation influences cerebral hemodynamics, we hypothesized that it would affect cerebral venous contrast in SWI.

Materials And Methods: SWI (125 examinations) of 26 patients (age, 2-16 years) was reviewed in this study.

Altered activation in association with reward-related trial-and-error learning in patients with schizophrenia.

In patients with schizophrenia, the ability to learn from reinforcement is known to be impaired. The present fMRI study aimed at investigating the neural correlates of reinforcement-related trial-and-error learning in 19 schizophrenia patients and 20 healthy volunteers. A modified gambling paradigm was applied where each cue indicated a subsequent number which had to be guessed.

Reduced cortical thickness in first episode schizophrenia.

Objective: Previous morphometric studies are suggesting altered cortical thickness mainly in prefronto-temporal regions in first episode schizophrenia. In an extension of these earlier studies, we used an entire cortex vertex-wise approach and an automated clustering for the detection and exact quantification of cortical thickness alterations in first episode schizophrenia.

Methods: A group of 54 patients with first episode schizophrenia according to DSM-IV and 54 age and gender matched healthy control subjects were included.

Disrupted white matter integrity of corticopontine-cerebellar circuitry in schizophrenia.

Evidence for white matter abnormalities in patients with schizophrenia is increasing. Decreased fractional anisotropy (FA) in interhemispheric commissural fibers as well as long-ranging fronto-parietal association fibers belongs to the most frequent findings. The present study used tract-based spatial statistics to investigate white matter integrity in 35 patients with schizophrenia and 35 healthy volunteers.

Extracerebellar MRI-lesions in ataxia telangiectasia go along with deficiency of the GH/IGF-1 axis, markedly reduced body weight, high ataxia scores and advanced age.

Ataxia telangiectasia (AT) is a rare autosomal recessive disorder characterized by progressive ataxia, neurodegeneration, immunodeficiency, and cancer predisposition. Pathoanatomical studies reported a degeneration of cerebellar Purkinje cells as the striking feature of the disease. Although recent studies suggested the involvement of extracerebellar structures such as the brainstem and basal ganglia, this has rarely been studied in human AT.

Psychopathological correlates of the entorhinal cortical shape in schizophrenia.

Animal experiments have shown that early developmental lesions of the entorhinal cortex lead, after a prolonged interval, to an enhanced mesolimbic dopamine release and an increased locomotor activity in rats. Hence, disturbed shape of the entorhinal cortex might indicate maturational abnormalities relevant for psychotic symptoms in schizophrenia. We used an automated surface-based MRI method to perform a region of interest analysis of entorhinal cortical surface area, folding and thickness in 59 patients with schizophrenia and 59 healthy controls.

Actinomyces in chronic granulomatous disease: an emerging and unanticipated pathogen.

Background: Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system that causes defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections, mostly by catalase-producing organisms. We report for the first time, to our knowledge, chronic infections with Actinomyces species in 10 patients with CGD. Actinomycosis is a chronic granulomatous condition that commonly manifests as cervicofacial, pulmonary, or abdominal disease, caused by slowly progressive infection with oral and gastrointestinal commensal Actinomyces species.

Time-resolved functional 1H MR spectroscopic detection of glutamate concentration changes in the brain during acute heat pain stimulation.

Non-invasive in vivo detection of cortical neurotransmitter concentrations and their changes in the presence of pain may help to better understand the biochemical principles of pain processing in the brain. In the present study acute heat pain related changes of the excitatory neurotransmitter glutamate were investigated in the anterior insular cortex of healthy volunteers by means of time-resolved functional proton magnetic resonance spectroscopy ((1)H-MRS). Dynamic metabolite changes were estimated with a temporal resolution of five seconds by triggering data acquisition to the time course of the cyclic stimulus application.

Identification of severe combined immunodeficiency by T-cell receptor excision circles quantification using neonatal guthrie cards.

Objective: To assess the feasibility of T-cell receptor excision circles (TRECs) quantification for neonatal mass screening of severe combined immunodeficiency (SCID).

Study Design: Real-time PCR based quantification of TRECs for 471 healthy control patients and 18 patients with SCID with various genetic abnormalities (IL2RG, JAK3, ADA, LIG4, RAG1) were performed, including patients with maternal T-cell engraftment (n = 4) and leaky T cells (n = 3).

Results: TRECs were detectable in all normal neonatal Guthrie cards (n = 326) at the levels of 10(4) to 10(5) copies/microg DNA.

Restoration of NET formation by gene therapy in CGD controls aspergillosis.

Chronic granulomatous disease (CGD) patients have impaired nicotinamide adenine dinucleotide phosphate (NADPH) oxidase function, resulting in poor antimicrobial activity of neutrophils, including the inability to generate neutrophil extracellular traps (NETs). Invasive aspergillosis is the leading cause of death in patients with CGD; it is unclear how neutrophils control Aspergillus species in healthy persons. The aim of this study was to determine whether gene therapy restores NET formation in CGD by complementation of NADPH oxidase function, and whether NETs have antimicrobial activity against Aspergillus nidulans.

Altered error-related activity in patients with schizophrenia.

Deficits in working memory (WM) and executive cognitive control are core features of schizophrenia. However, findings regarding functional activation strengths are heterogeneous, partly due to differences in task demands and behavioral performance. Previous investigators proposed integrating these heterogeneous findings into a comprehensive model of cortical inefficiency assuming the inverted U-shaped relationship between performance and neuronal activation to be shifted in patients.